Biotechnology Research Institute for Drug Discovery
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Research Achievements

The research achievements of the Biotechnology Research Institute for Drug Discovery.

Contents



Significant Achievements

Targeting the glycans on pancreatic cancer cell surface with lectin-drug conjugate (Japanese)
- Development of novel anticancer treatment as a post-antibody drug -

•  Glycans strongly expressing on surface of pancreatic cancer cell, a representative refractory cancer, and lectins (protein with glycan-binding ability) specifically recognizing the glycans were identified.
•  Safety of lectin-drug conjugate (LDC) consisting of fused lectin and anticancer drug was confirmed to be free of adverse effect such as coagulation in mice.
•  Treatment of various pancreatic cancer models is possible with the new approach, in which lectins target glycans covering the outermost coating of cell.
•  Feasibility of lectins as a drug carrier was suggested to be cost effective post-antibody drug that can compensate expensive antibody therapeutics.

Date: 2017/9/26
Group/Lab: Cellular Glycome-targeted Technology Research Group
Reference: A novel therapeutic strategy for pancreatic cancer: targeting cell surface glycan using rBC2LC-N lectin-drug conjugate (LDC)
Mol Cancer Ther. 2017 Sep 22. [Epub ahead of print]
Clarification of the new reaction mechanism for sulfur modification in cell (Japanese)
- A step toward research of functional control of mitochondria -

•  A novel identification of sulfur modification enzyme relating to the functions of mitochondria requires an unstable iron-sulfate cluster that degrade by oxygen exposure.
•  Proposal of mechanism for sulfate transfer reaction of tRNA related to iron sulfate cluster.
•  It is an important discovery for elucidation of mechanism for controlling energy production in mitochondria.

Date: 2017/4/25
Group/Lab: Leading-edge Biotechnology Research Group
Reference: Biochemical and structural characterization of oxygen-sensitive 2-thiouridine synthesis catalyzed by an iron-sulfur protein TtuA
Proc Natl Acad Sci U S A. 2017 May 9;114(19):4954-9
Decoding complex genome of African clawed frog (Japanese)
- Closer to the unsolved secret of “complete genome duplication”, the driving force of evolution to vertebrate -

•  Xenopus laevis has "complete genome duplication" considered to be resulted from crossbreeding of its two progenitors. We have clarified all the structure of its complicated genome, which was the last genome information of major model animals being decoded.
•  Two kinds of genomes (subgenomes) succeeded from the ancestor species were identified, and the evolution after "complete genome duplication" happened 18 million years ago was elucidated for the first time.
•  Not only this genome information would be a great contribution to the progress of life science, it will become the key and the Rosetta Stone to solve the secret of "complete genome duplication" considered to happen along with the birth of vertebrate.

Date: 2016/10/20
Group/Lab: Stem Cell Engineering Research Group
Reference: Genome evolution in the allotetraploid frog Xenopus laevis
Nature. 2016 Oct 19;538(7625):336-43

Development of Technology to Evaluate the Differentiation Ability of Human Mesenchymal Stem Cells
- Contributing to practical application of regenerative medicine with simple and rapid evaluation -

•  Four types of lectins demonstrated high reactivity to human mesenchymal stem cells which have strong ability to differentiate
•  Confirmed that it is possible to evaluate the differentiation ability of human mesenchymal stem cells with the reactivity of these lectins
•  Expected to be applied to quality management in the manufacturing process of human mesenchymal stem cells

Date: 2016/4/4
Group/Lab: Glycan Lectin Engineering Research Group, Stem Cell Engineering Research Group
Reference: α2-6 sialylation is a marker of the differentiation potential of human mesenchymal stem cells
Glycobiology. 2016 Dec;26(12):1328-37
Development of COSMOS: Algorithm for large-scale and highly accurate detection of genomic structural variations (Japanese)
- Expected to contribute for elucidation of malignant transformation and early detection of cancer -

•  Rapidly and accurately compares genome big data of normal and cancer cells obtained by massive parallel DNA sequencing
•  Precisely detects structure variations of tissue samples containing cancer cells even at a low level.
•  Detects cancer-specific DNA variations at an early stage, which enables appropriate choice of therapeutic measures.

Date: 2016/2/2
Group/Lab: Computational Functional Genomics Research Group
Reference: COSMOS: accurate detection of somatic structural variations through asymmetric comparison between tumor and normal samples
Nucleic Acids Res. 2016 May 5;44(8):e78
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Development of regenerative medicine-related products by DNA Chip Research Inc., Zenoaq Resource Co., Ltd., and Taiyo Nippon Sanso Corporation in the collaboration research project in which Stem Cell Engineering Research Group participated.

Evaluation, maintenance, and transfer technology systems were successfully developed in the NEDO/AMED collaboration research project in which the Stem Cell Evaluation Technology Research Association contracted. The Stem Cell Engineering Research Group (group leader Ito and senior researcher Onuma) contributed to the development.

Date: 2015/10/8
Group/Lab: Stem Cell Engineering Research Group
Interaction mapping of outer membrane translocator TOM complex reveals the mechanism of protein translocation into mitochondria (Japanese)

The protein translocator of the outer membrane (TOM) complex imports most mitochondrial proteins, however, its architecture is unknown. Using a cross-linking approach and structure modeling, we mapped the interactions of Tom40 with other subunits or preproteins, revealing trimeric TOM complex architecture and different transport paths for preproteins through the Tom40 channel. This discovery was the product of collaborative research with Professor Toshiya Endo (Nagoya University/Kyoto Sangyo University), Professor Trevor Lithgow (Monash University) and AIST researchers Kenichiro Imai, Yoshinori Fukasawa, Kentaro Tomii and Paul Horton.

Date: 2015/9/25
Group/Lab: Computational Functional Genomics Research Group
Reference: Molecular architecture of the active mitochondrial protein gate
Science Magazine. 2015 Sep 25;349(6255):1544-48
Generation of stomach tissue from mouse embryonic stem cells

A stem cell culture technology to induce stomach tissues secreting digestive enzymes and gastric acid was developed. This technology was developed as an achievement of a collaborative study of Chief senior researcher Kurisaki and Researcher Ninomiya (Stem Cell Engineering Research Group, AIST), AIST Fellow Asashima, Noguchi and Sekine, Professor Wang (Graduate School of Life and Environmental Sciences, University of Tsukuba), Associate professor Komazaki (Saitama Medical University).

Date: 2015/8/4
Group/Lab: Stem Cell Engineering Research Group
Reference: Generation of stomach tissue from mouse embryonic stem cells
Nat Cell Biol. 2015 Aug;17(8):984-93
Development of a Technology to Eliminate Tumorigenic Human Induced Pluripotent Stem Cells and Embryonic Stem Cells from Transplanting Cells
- Can reduce tumorigenicity risks in regenerative medicine -

•  Lectin that specifically binds to human induced pluripotent stem cells and embryonic stem cells was fused with a toxin.
•  Human induced pluripotent stem cells and embryonic stem cells can be selectively eliminated by simple addition of the fusion protein to culture medium.
•  This technology is expected to improve the safety of regenerative medicine using human induced pluripotent stem cells and embryonic stem cells.

Date: 2015/4/10
Effect of lectin-toxin fusion protein on hiPSCs
Group/Lab: Stem Cell Engineering Research Group, Glycan Lectin Engineering Research Group
Reference: Generation of stomach tissue from mouse embryonic stem cells
Nat Cell Biol. 2015 Aug;17(8):984-93
Testing the safety of transplanting cells using cell culture supernatants [ PDF:494KB ]
- Improve the safety of regenerative medicine -

Date: 2014/4/1
Detect residual human iPS/ES cells using cell culture supernatants
Group/Lab: Glycan Lectin Engineering Research Group
Reference: A medium hyperglycosylated podocalyxin enables noninvasive and quantitative detection of tumorigenic human pluripotent stem cells
Sci Rep. 2014 Feb 12;4:4069
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